Identification of gene markers based on well validated and subcategorized stressed animals for potential clinical applications in PTSD

Abstract

Post-traumatic stress disorder (PTSD) is a complex mental disorder that can develop in response to traumatic experiences. The molecular mechanisms underlying the pathology of PTSD are poorly understood, and this lack of knowledge hampers our ability to find superior therapeutic approaches to the treatment of this disorder. There are two main reasons for our lack of study in this area: here is no sufficiently validated animal model and lack of large-scale studies for the search of underlying molecular mechanisms. Thus, to promote research on PTSD (especially its molecular mechanisms) and to set molecular basis for searching novel medications of this disorder, large-scale, genome-wide interrogation of a significant amount of genes based upon a well validated animal model is demanded. We hypothesize that a significant number of genes are involved in PTSD. It is only with a large number of these genes identified in specific samples of PTSD-related population, and then it is possible for a sufficient understanding of the pathology at the molecular level of a PTSD, as well as for enhancing the PTSD's therapeutic and preventative strategies. Two prerequisites are needed for testing this hypothesis: (1) relative pure samples from a well validated animal model; and (2) genome-wide screening of PTSD molecular targets. For the animal model, we suggest to use the predator-exposure paradigm, in which rats are exposed to a predator, this model has previously been evaluated behaviorally well emulated the clinical symptoms of PTSD. For a better stringency, three criteria can be used to further validate this animal model: analogous (similarity of behavior), predictive (predictability of drug response) and biological mechanism (e.g., electrophysiological and pathological change in amygdala). For large-scale molecular target screening, the new microarray technology, which can profile expression of tens of thousands genes simultaneously, is the method of choice. The validity and practicability of this hypothesis and the strategy for its testing have been supported by our preliminary laboratory data.